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Lipid drop formation at the endoplasmic reticulum is crucial for proper fat storage
Electron micrograph of a primary rat hepatocyte shows the formation of nascent lipid drops from the endoplasmic reticulum.
Lipid Droplet Biology and Fatty Liver
Fatty liver, also called hepatic steatosis, has become the most common disease of the liver in the United States. Over 40% of Americans have a fatty liver, which can lead to liver fibrosis, inflammation called hepatitis, cirrhosis and cancer. Moreover, because the liver is a central detoxification organ, it is especially susceptible to damage from alcohol. Most heavy drinkers exhibit fatty liver, referred to as ethanol-induced hepatic steatosis. And 40% to 50% of these people can develop severe, life-threatening disease. The central organelle within the hepatocyte that stores excess fat is the lipid droplet (LD). Scores of different proteins control the formation and utilization of LDs. A deficit in LD breakdown is believed to play a central role in fatty liver disease.
The Membrane Trafficking in Disease Lab's goals are to define how:
- The hepatocyte targets different catabolic proteins to the LD surface to mediate LD breakdown.
- The mechanisms by which autophagolysosomes engulf LDs in a process, termed lipophagy, mediate catabolism.
- The mechanisms by which LDs-autophagolysosomes-mitochondria interact to expedite lipid catabolism.
- Alcohol alters LD composition, function and breakdown.
- Alcohol alters the association of LD-bound proteins that can contribute to normal fat catabolism and autophagy.